Dockres: a computer program that analyzes the output of virtual screening of small molecules.

Mezei M, Zhou MM - Source Code Biol Med (2010)

Bottom Line:
This paper describes a computer program named Dockres that is designed to analyze and summarize results of virtual screening of small molecules.Analysis of virtual screening by Dockres led to both active and selective lead compounds.Analysis of virtual screening was facilitated and enhanced by Dockres in both the authors' laboratories as well as laboratories elsewhere.

Affiliation: Department of Structural and Chemical Biology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, New York 10029, USA. Mihaly.Mezei@mssm.edu.

ABSTRACT

Background: This paper describes a computer program named Dockres that is designed to analyze and summarize results of virtual screening of small molecules. The program is supplemented with utilities that support the screening process. Foremost among these utilities are scripts that run the virtual screening of a chemical library on a large number of processors in parallel.

Methods: Dockres and some of its supporting utilities are written Fortran-77; other utilities are written as C-shell scripts. They support the parallel execution of the screening. The current implementation of the program handles virtual screening with Autodock-3 and Autodock-4, but can be extended to work with the output of other programs.

Results: Analysis of virtual screening by Dockres led to both active and selective lead compounds.

Conclusions: Analysis of virtual screening was facilitated and enhanced by Dockres in both the authors' laboratories as well as laboratories elsewhere.

Figure 1: Characterization of a docked pose of one ligand. In the first line, the free energy score (-8.3) is specified, followed by it multiplicity (m), the ligand file name (5669377-1), the molecular weight (MW), the number of hydrogen-bond donors and acceptors (HBd and HBa), the number of torsions (t), -NO2 groups (NO2) and rings (r). The second line specifies the pose number (84), the number of hydrogen bonds between the ligand and the protein (nHB), the ligand charge (q), the protein atom (atom and residue names and numbers) closest to the ligand (pa), the distance from the binding site (Rbs) and the chemical formula (F). The subsequent lines describe ligand-protein contacts: ligand atom (L) number and name - protein atom number, name, residue number and name. Contact is defined as pairs of ligand-protein atoms that are mutually proximal. In addition, the pose list is preceded by statistics giving the number of poses in different free-energy score range.

Mentions:
The extracted poses are sorted by their scores calculated by Autodock. Figure 1 shows a typical record describing a pose (ligand properties, contacts, etc.). The user has an option of selecting the number of top scoring poses to list; another option is to limit each ligand to a single pose in this list. Besides the list of top-scoring poses and their characterizations, the docked complexes can be extracted into either a single PDB file with all the selected poses or separate PDB files, each containing a complex with a single ligand.

Figure 1: Characterization of a docked pose of one ligand. In the first line, the free energy score (-8.3) is specified, followed by it multiplicity (m), the ligand file name (5669377-1), the molecular weight (MW), the number of hydrogen-bond donors and acceptors (HBd and HBa), the number of torsions (t), -NO2 groups (NO2) and rings (r). The second line specifies the pose number (84), the number of hydrogen bonds between the ligand and the protein (nHB), the ligand charge (q), the protein atom (atom and residue names and numbers) closest to the ligand (pa), the distance from the binding site (Rbs) and the chemical formula (F). The subsequent lines describe ligand-protein contacts: ligand atom (L) number and name - protein atom number, name, residue number and name. Contact is defined as pairs of ligand-protein atoms that are mutually proximal. In addition, the pose list is preceded by statistics giving the number of poses in different free-energy score range.

Mentions:
The extracted poses are sorted by their scores calculated by Autodock. Figure 1 shows a typical record describing a pose (ligand properties, contacts, etc.). The user has an option of selecting the number of top scoring poses to list; another option is to limit each ligand to a single pose in this list. Besides the list of top-scoring poses and their characterizations, the docked complexes can be extracted into either a single PDB file with all the selected poses or separate PDB files, each containing a complex with a single ligand.

Bottom Line:
This paper describes a computer program named Dockres that is designed to analyze and summarize results of virtual screening of small molecules.Analysis of virtual screening by Dockres led to both active and selective lead compounds.Analysis of virtual screening was facilitated and enhanced by Dockres in both the authors' laboratories as well as laboratories elsewhere.

Affiliation:
Department of Structural and Chemical Biology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, New York 10029, USA. Mihaly.Mezei@mssm.edu.

ABSTRACT

Background: This paper describes a computer program named Dockres that is designed to analyze and summarize results of virtual screening of small molecules. The program is supplemented with utilities that support the screening process. Foremost among these utilities are scripts that run the virtual screening of a chemical library on a large number of processors in parallel.

Methods: Dockres and some of its supporting utilities are written Fortran-77; other utilities are written as C-shell scripts. They support the parallel execution of the screening. The current implementation of the program handles virtual screening with Autodock-3 and Autodock-4, but can be extended to work with the output of other programs.

Results: Analysis of virtual screening by Dockres led to both active and selective lead compounds.

Conclusions: Analysis of virtual screening was facilitated and enhanced by Dockres in both the authors' laboratories as well as laboratories elsewhere.